Understanding Chronic Inflammation's Role in Aging and Longevity

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• Inflammation and Longevity Connection
• Chronic Inflammation in Aging
• Dynamic Range in Biological Pathways
• mTOR and Rapamycin's Role
• Interventions for Long-Term Health
• Full Transcript

Inflammation and Longevity Connection

Dr. Brian Kennedy, MD, explores the critical link between systemic inflammation and the aging process. He explains that reducing chronic, low-grade inflammation may be a powerful strategy for promoting longevity. Dr. Anton Titov, MD, initiates this discussion by questioning if common anti-inflammatory agents, like low-dose aspirin, could slow aging. Aspirin's long-term use is associated with a reduced risk of certain cancers, suggesting a profound connection between inflammation control and healthspan.

Chronic Inflammation in Aging

Dr. Brian Kennedy, MD, clarifies that inflammation is not inherently bad. Dr. Brian Kennedy, MD, states that acute inflammation is a vital, healthy response to injury or infection. This response is crucial for healing wounds and eliminating pathogens. The central problem of aging is the failure to resolve this inflammatory state. Instead of turning off, inflammatory signals persist at a low to moderate grade. This chronic inflammation is unhealthy for tissues over many years and decades.

Dynamic Range in Biological Pathways

A key concept Dr. Brian Kennedy, MD, introduces is the loss of "dynamic range" with age. Young individuals possess a high degree of adaptability in their biological systems. Their inflammatory pathways can turn on powerfully when needed and then shut off completely. Aging erodes this ability, leaving pathways like inflammation stuck in a semi-activated state. This loss of flexibility makes an older body less resilient to physiological challenges. Maintaining this youthful dynamic range is a primary goal of longevity research.

mTOR and Rapamycin's Role

The conversation with Dr. Anton Titov, MD, turns to the mTOR pathway, a central regulator of cell growth and metabolism. Dr. Brian Kennedy, MD, explains that, like inflammation, mTOR is not a pathway that should simply be turned off. It needs to be active at specific times for proper cellular function. The issue in aging is elevated basal mTOR signaling. He proposes that low-dose rapamycin works not by shutting down mTOR, but by suppressing its age-related elevation. This intervention helps preserve the pathway's healthy dynamic range, which is good for long-term health.

Interventions for Long-Term Health

Dr. Brian Kennedy, MD, suggests that the most successful lifespan-extending interventions function by restoring dynamic range. This principle applies to multiple biological pathways beyond just inflammation and mTOR. The goal is not to chronically suppress a pathway but to recalibrate it to function as it did in youth. This approach allows the body to respond appropriately to stimuli again. Dr. Brian Kennedy, MD, notes that while not universally agreed upon, this framework for how rapamycin and similar compounds work is a compelling model for promoting longevity.

Full Transcript

Dr. Anton Titov, MD: Inflammation and longevity. Can reducing inflammation contribute to longevity? For example, can aspirin help slow aging in low doses? Aspirin does seem to reduce systemic inflammation, even though it's not overly noticeable at low doses. But over the course of years and possibly decades, it does have a reduction effect on certain cancers.

What is the connection between low-grade inflammation and longevity?

Dr. Brian Kennedy, MD: We could talk about NSAIDs and chronic use and long-term health for the whole show. I'm not an expert on that. I think there are benefits to curtailing chronic inflammation with aging. We tend to think of inflammation as a bad thing, but it's not right when you have a wound or something like that. You have an inflammatory response to an infection.

That inflammatory response contributes to healing the wound or getting rid of the foreign agent that's infecting you. The problem is, when you're young, when that's over, you turn the inflammatory signals back down and go back to a healthy state.

During aging, you see an increase in chronic inflammation, and that's really the problem. You have sort of low-grade or even moderate-grade inflammatory signaling going on all the time, or most of the time. That's not healthy for your tissues over the long run.

I think it illustrates a point with aging: we tend to say we need to turn this up or turn it down, like the mTOR pathway. We need to turn it down. But the truth is, what we need to do is maintain the dynamic range that young people have. You need inflammation on, but it should be on and off when it should be off. The problem is inflammation is not off anymore.

Losing that dynamic range makes you less adaptable to challenges that happen to your body. I think most of these pathways we're talking about, the interventions that extend lifespan, do so by helping to keep the dynamic range for these pathways.

mTOR is an example; you want mTOR on at times too. So a relatively low dose of rapamycin suppresses the elevation and basal mTOR signaling with aging and keeps that range. I think that is good for long-term health. I'm not sure everyone agrees on that.

Dr. Anton Titov, MD: We'll discuss it a little bit later specifically, because I have a few questions on rapamycin in particular.